FDA s Draft Guidance Request for Quality Metrics: What All Drug and Biologics Manufacturers Need to Know June 2017

Transcription

1 FDA s Draft Guidance Request for Quality Metrics: What All Drug and Biologics Manufacturers Need to Know June 2017

2 Discussion Topics Quality Concepts The Journey The Guidance Details Industry Responses Summary 2

3 Quality Metrics Concepts 3

4 Understanding Quality Performance FDA Vision: A maximally efficient, agile, flexible pharmaceutical manufacturing sector that reliably produces high quality drug products without extensive regulatory oversight. Janet Woodcock, October

5 Definition of Quality From ICH Q10: Pharmaceutical Quality System The degree to which a set of inherent properties of a product, system or process fulfills requirements From ICH Q9: Quality Risk Management Definition of Quality: The degree to which a set of inherent properties of a product, system or process fulfills requirements From ICH Q6: Specifications Definition of Quality: The suitability of either a drug substance or drug product for its intended use. This term includes such attributes as the identify, strength, and purity. 5

6 Current Quality Concepts ICH Q10: Pharmaceutical Quality System Senior management has the ultimate responsibility to ensure an effective pharmaceutical quality system is in place to achieve the quality objectives, and that roles, responsibilities, and authorities are defined, communicated and implemented throughout the company. 6

7 ICH Q10 Management Principles Participate in the design, implementation, monitoring and maintenance of an effective pharmaceutical quality system Demonstrate strong and visible support for the pharmaceutical quality system and ensure its implementation throughout their organization Ensure a timely and effective communication and escalation process exists to raise quality issues to the appropriate levels of management Define individual and collective roles, responsibilities, authorities and interrelationships of all organizational units related to the pharmaceutical quality system. Ensure these interactions are communicated and understood at all levels of the organization. Conduct management reviews of process performance and product quality and of the pharmaceutical quality system Advocate continual improvement Commit appropriate resources 7

8 Quality Metrics as a Tool Demonstrated Quality Performance = Privileges Less frequent inspection Preferred handling of Post Approval Changes 8

9 Quality Metrics as a Tool (cont ) Metrics Create a Dialog Within a Company to: Drive continuous improvement Provide early detection of control drifts Focus resources on a particular area Ensure a stable supply of drug product. 9

10 10

11 Linking Drug Shortages and Quality Metrics Food and Drug Administration Safety and Innovation Act (FDASIA) Signed into Law on July 9, 2012 Pertinent Sections of the Act Title VII Section 705 and 706 Title X Section 506C Federal Register Notice 11

12 Title VII Section 705: Risk-based Inspectional Frequency Risk Factors The compliance history of the establishment. The record, history, and nature of recalls linked to the establishment. The inherent risk of the drug manufactured, prepared, propagated, compounded, or processed at the establishment. 12

13 Title VII Section 705 (cont ) Risk-based Inspectional Frequency: Risk Factors (cont ) The inspection frequency and history of the establishment, including whether the establishment has been inspected pursuant to section 704 within the last 4 years. Whether the establishment has been inspected by a foreign government or an agency of a foreign government recognized under section 809. Any other criteria deemed necessary and appropriate by the Secretary for purposes of allocating inspection resources. 13

14 Title VII Section 706: Records for Inspection Any records or other information that the Secretary may inspect under this section from a person that owns or operates an establishment that is engaged in the manufacture, preparation, propagation, compounding, or processing of a drug shall, upon the request of the Secretary, be provided to the Secretary by such person, in advance of or in lieu of an inspection, within a reasonable timeframe, within reasonable limits, and in a reasonable manner, and in either electronic or physical form, at the expense of such person. 14

15 Title X: Drug Shortages Section 506C: Discontinuation or Interruption in the Production of Life-Saving Drugs Discontinuation or Shortage Notification 6 Months Prior or as Soon as Practical for: Life Supporting Medicines Life Sustaining Medicines Medicines Used in Prevention or Treatment of Debilitating Disease 15

16 Title X: Drug Shortages (cont ) Section 506C-1: Annual Reporting on Drug Shortages Requires Annual Reports to Congress starting in 2013 Specifying the Number of Manufacturers Submitting Drug Shortage Notifications Describing Communication Between the FDA Field Investigators and the Center for Drug Evaluation and Research s Office of Compliance and Drug Shortage Program Lists the Major Actions Taken to Prevent or Mitigate the Drug Shortages 16

17 Federal Register Notice 12 Feb 13 Summary: To assist the FDA or Agency in drafting a strategic plan on drug shortages as required by the FDASIA SEC. 506D. COORDINATION; TASK FORCE AND STRATEGIC PLAN FDA formed an internal Drug Shortages Task Force (Task Force) to develop and implement the drug shortages strategic plan To assist in the evaluation of product manufacturing quality, FDA is exploring the broader use of manufacturing quality metrics 17

18 Federal Register Notice (cont ) Questions Asked of Industry: What metrics do manufacturers currently use to monitor production quality? To what extent do purchasers and prescribers use information about manufacturing quality when deciding how to purchase or utilize products? What kinds of manufacturing quality metrics might be valuable for purchasers and prescribers when determining which manufacturers to purchase from or which manufacturers' products to prescribe? What kinds of manufacturing quality metrics might be valuable for manufacturers when choosing a contract manufacturer? How frequently would such metrics need to be updated to be meaningful? 18

19 The Guidance 19

20 Metrics Journey PDA Metric Conf #1 PDA Culture Metrics Survey PDA Q Culture Assessment Pilot Industry White Papers Published PDA Metric Conf #2 PDA Metric Conf #3 PDA Metric Conf #4 Initial Industry Responses ISPE Pilot Announced ISPE Pilot Results Wave 1 ISPE Pilot Results Wave 2 Feb 2013 May Aug Nov Feb 2014 May Aug Nov Feb 2015 May Aug Nov Feb Nov 2016 May Aug Nov Feb 2017 May FR Notice Requesting Metrics to Prevent Drug Shortages Brookings Stakeholder Meeting Metrics of Potential Interest FDA Draft Guidance (rev 1) FDA Technical Conformance Guidance FDA Draft Guidance (rev 2) 20

21 Guidance Details Original Proposed Metrics Lot Acceptance Rate Product Quality Complaint Rate Invalidates OOS Rate Annual Product Review or Product Quality Review on Time Rate 21

22 Guidance Details (continued) Optional Proposed Metrics Measuring Quality Culture Measuring Senior Management Engagement CAPA Effectiveness Process Capability/Performance 22

23 Guidance Details (continued) Optional Proposed Metrics A yes or no value of whether the establishment s management calculated a process capability or performance index for each critical quality attribute (CQA) as part of that product s APR or PQR. A yes or no value of whether the establishment s management has a policy of requiring a corrective action or preventive action (CAPA) at some lower process capability or performance index. If yes to the above question what is the process capability or performance index that triggers a CAPA? If no to the above question please do not respond. 23

24 Guidance Details (continued) Current Proposed Metric Lot Acceptance Rate Product Quality Complaint Rate Invalidated OOS Rate 24

25 Guidance Details (continued) Who Reports Owners and operators of each establishment that is engaged in the manufacture, preparation, propagation, compounding, or processing of a covered drug product, or an API used in the manufacture of a covered drug product, may submit quality metrics data. 25

26 Guidance Details (continued) Reporting Metrics Time Span Definition: Data segmented on a quarterly basis throughout a single calendar year. Voluntary Reporting Participation in this voluntary reporting phase of the program also demonstrates a commitment to increasing transparency between industry and FDA and a contribution to improving quality monitoring throughout the industry. 26

27 Guidance Details (continued) FDA Use of Metrics establish a signal detection program as one factor in identifying establishments and products that may pose significant risk to consumers; identify situations in which there may be a risk for drug supply disruption; improve the effectiveness of establishment inspections; and improve FDA s evaluation of drug manufacturing and control operations 27

28 WELLNESS FOR BUSINESS Lessons Learned 28

29 WELLNESS FOR BUSINESS PDA Activities PDA s Quality Metric: Look Back Organized four conferences focused on Metrics Published Metric White Paper Provided three sets of Comments Original Draft Guidance Technical Guidance Revised Guidance Presented at FDA Public Metric Meeting ( 15) Spun off a Quality Culture Task Force 29

30 WELLNESS FOR BUSINESS Moving Forward PDA Quality Metric Task Force: Future Remain Nimble and Flexible Provide comments / feedback on draft Metric documents Continue to support Metric implementation across the industry Explore future conference opportunities Dialog with FDA on their program 30

31 WELLNESS FOR BUSINESS Docket Comments 31

32 WELLNESS FOR BUSINESS Comments to Revised Draft Guidance March Docket Submissions 83 to first version of guidance 12 Associations 10 Individual Firms 1 Hospital Group 1 Academic Institution 1 Individual 32

33 WELLNESS FOR BUSINESS Industry Groups have Individual Interests Medical Gases, Plasma Products, Excipients, and OTCs, want their products excluded. CMOs want to report data to License Holders who would then submit to FDA. BIO AAM (formerly GpHA) and PhRMA asking for entire program to pause 33

34 WELLNESS FOR BUSINESS Key Points in PDA Response Define success criteria for voluntary phase Q&A Document developed to clarify definitions Focus on metric/data trends rather than comparison of absolute values Ask FDA to advocate for harmonization efforts Recognition list of all voluntary participants 34

35 WELLNESS FOR BUSINESS Common Themes in Docket Responses Support for FDA objectives Acknowledgement that FDA listened and acted upon industry concerns in second draft Revised Draft doesn t resolve all the issues Metrics commonly used by individual firms but challenges with standardized program Many questions on calculations, definitions, datasets 35

36 WELLNESS FOR BUSINESS Reporting by Site or Product Site Metrics align with FDA Inspectional Readiness goals Product Metrics align with ability to predict and reduce drug shortages The product-related metrics necessary to predict and alleviate drug shortage situations might be at odds with the site-related ones that could assess quality at a facility level. It is unclear how the metrics identified in this Guideline will lead to insights that will help predict, and possibly mitigate, drug shortages. PDA supports reporting by both product and site and the license holder be responsible for submission. 36

37 WELLNESS FOR BUSINESS CMO Reporting Don t see benefit to their firms Don t file PACs Majority of site audits are by clients not FDA Some metrics don t apply to API only sites Option of site or product reporting may double their work Don t have visibility to metrics in other steps of supply chain i.e. complaints Current Quality Agreements will likely need to be renegotiated. 37

38 WELLNESS FOR BUSINESS External Interest in Metrics Hospital Organization Docket comment Reviewing a manufacturers quality records that are available is a key component when selecting contracted vendors for our health systems. Software Vendors with Big Data Systems The JD Powers for pharmaceuticals 38

39 WELLNESS FOR BUSINESS Internal Use vs. Submission Agility: Local metrics defined based on local needs and change and adapt to process improvement and situations. Verification: The requirement for 100% verifiable data with precision needed for a government submission that is required through this initiative would increase human and system resources to support it without necessarily adding significant additional value. Ownership: Quality Unit use of metrics vs. Reg Affairs use in submissions 39

40 WELLNESS FOR BUSINESS Information Disclosure and Security Need clarity on whether metrics is considered a voluntary submission and therefore protected from FOIA. Data reveals production volumes considered proprietary information Concern over electronic security of data within FDA systems Will metrics data be shared with other Health Authorities what are security precautions there? 40

41 WELLNESS FOR BUSINESS Lessons Learned Metrics is a very complex topic, fraught with unintended consequences. Trending is most important Optimizing a metric program takes time to evolve Metrics has to be combined with a strong Quality Culture to be meaningful Focusing on a metric can compromise its utility Finding forward looking metrics is very difficult 41

42 WELLNESS FOR BUSINESS 42

43 WELLNESS FOR BUSINESS 43